Studies on the total synthesis and evaluation of antitumor antibiotics including isochrysohermidin, streptonigrone, fredericamycin A, rubrolone, bleomycin A2 and key structural analogs are detailed. In the course of the studies, the investigation, development, and implementation of: (l) heteroaromatic azadiene Diels-Alder reactions, (2) the LUMO(diene)- controlled Diels-Alder reactions of N-sulfonyl-l-aza-l,3-butadienes, (3) the intramolecular Diels-Alder reactions of 0-methyl alpha-beta- unsaturated oximes, (4) the thermal reactions of cyclopropenone ketals including those of reversibly generated pi-delocalized singlet vinylcarbenes, (5) chromium carbene complex benzannulation reactions, and (6) acyl radical alkene addition reactions will continue to be pursued and provide the opportunity to comprehensively extend past studies. An additional application of the synthetic methodology to the preparation of pyridoxol is described. The proposed studies include the examination of antitumor antibiotics that mediate their cellular effects through sequence selective duplex DNA binding and modification and provide well-defined problems on the design, preparation, and evaluation of synthetic, mechanism-based antitumor agents in which fundamental studies of their structural responsible for DNA binding affinity, selectivity, and functional reactivity may be addressed.